Pendred's Syndrome: Deficiency in Iodide Transport

Pendred's syndrome is an autosomal recessive disorder defined by the triad of congenital deafness, goiter, and a partial defect in iodide organification. Under conditions of normal iodide intake, patients with Pendred's syndrome are usually euthyroid, but if the nutritional iodide supply is scarce, overt hypothyroidism may develop. Pendred's syndrome is caused by mutations in the PDS/SLC26A4 gene, which encodes the anion transporter pendrin. Pendrin is predominantly expressed in the inner ear, the thyroid, and the kidney. In thyroid follicular cells, pendrin localizes to the apical membrane. Pendrin is an exchanger of chloride and bicarbonate, and it is involved in apical efflux of iodide in thyroid follicular cells. In addition to pendrin, at least one other apical iodide channel can mediate apical iodide efflux in thyroid follicular cells. Pendrin is expressed in type B intercalated cells in the renal collecting duct and involved in chloride/bicarbonate exchange. Pendrin knockout mice have a decreased rise in blood pressure in response to a high salt diet or treatment with aldosterone analogs. In the inner ear, pendrin is essential for generation of the endocochlear potential. In the absence of functional pendrin, the endolymphatic system undergoes a progressive enlargement that results in severe degeneration of sensory cells and otoconia.